Method of delivering active material within hydrogel microbeads

ABSTRACT

A method of delivering active material using microbeads comprising droplets of active material entrained in a hydrophilic matrix. Compositions comprising the microbeads may be sprayable. The microbeads of the invention may be controllable by exposing the microbeads to high or low humidity or moisture.

FIELD OF THE INVENTION

[0001] The invention relates broadly to immobilization and release ofactive material within hydrogel microbeads. The hydrogel microbeads canbe used to immobilize water soluble and water insoluble actives such asoils, fragrances, lubricants, and agricultural chemicals such aspheromones, herbicides, insecticides and pesticides.

BACKGROUND

[0002] Methods of eliminating unwanted pests from orchards, crops andforests frequently entail the use of organophosphate insecticides.Alternative methods involve insect mating disruption, where insectpheromones are used to control pests and protect agricultural crops. Ininsect mating disruption methods, the mating pheromone plume of a femaleinsect is typically masked with other pheromone point sources. Thisreduces the likelihood of a male insect finding a female, andsubsequently disrupts and reduces larvae production. The insectpopulation of the next generation is thus decreased, as well aspotential crop damage.

[0003] Conventional sprayable pheromone formulations are generallyprovided in liquid filled microcapsules containing an active. Typically,the microcapsules have a polyurea membrane that can be formed using aninterfacial process involving an isocyanate and an amine.Microencapsulation by this method has been descibed for example in U.S.Pat. No. 4,487,759 (Nesbitt et al., 1984). These polyurea membranesallow actives to be released into the atmosphere for up to a total of2-3 weeks for most insect pheromones.

[0004] Use of interfacial condensation to encapsulate substances such aspharmaceuticals, pesticides and herbicides is taught in U.S. Pat. No.3,577,515. The encapsulation process involves two immiscible liquidphases (typically water and an organic solvent), one being dispersed inthe other by agitation, and the subsequent polymerization of monomersfrom each phase at the interface between the bulk (continuous) phase,and the dispersed droplets. Polyurethanes and polyureas are materialssuitable for producing the microcapsules. The microcapsules comprise apolymeric sphere and a liquid center, ranging from 30 micron to 2 mm indiameter, depending on monomers and solvents used.

[0005] Highly viscous and thickened hydrogels have been used to deliverpheromones, fragrances and other non-water soluble actives. U.S. Pat.No. 4,755,377, for example, describes a process of encapsulating perfumeor fragrant material within an aqueous-based gel composition. Theresulting material is in the form of a highly viscous semi-solid. U.S.Pat. No. 5,645,844 describes the use of chitosan paste for delivery ofpheromones to disrupt insect mating, where the material can be dispensedby an apparatus such as a caulking gun. Due to their thickness and highviscosity, these materials, however, are generally unsprayablecompositions.

[0006] Most hydrogels are safe and non-toxic to humans. Hydrogels havebeen used for encapsulation of biological materials whereby theformulation is non-lethal to the viability of cells, proteins, andrelated materials. U.S. Pat. No. 4,689,293, describes the process ofencapsulating living tissue or cells in alginate beads. Theencapsulation shell permits the passage of materials and oxygen to thecells and permits the diffusion of the metabolic by-products from thegel.

SUMMARY OF THE INVENTION

[0007] A method of delivering active material using a plurality ofmicrobeads suspended in solution is provided, where the microbeadscomprise a hydrophilic matrix having droplets of active materialentrained therein. Furthermore, the matrix is capable of immobilizing abroad spectrum of active materials, either water soluble or non-watersoluble. In one aspect of the invention, the hydrophilic matrix may bemade from a naturally occurring material to provide an environmentallyfriendly microbead.

[0008] In another aspect of the invention, the active entrained in thematrix diffuses from the hydrophilic matrix and is released into theenvironment over an extended period.

[0009] In yet another aspect, the microbeads are capable of re-hydratingafter an initial dehydration and release of active. Thus, the releaseand longevity of the active can be controlled by adjusting the humidityof the environment in which the microbeads have been delivered.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010]FIG. 1 is a cross-sectional illustration depicting a preferredembodiment of a microbead of the invention.

[0011]FIG. 2 is a graph from data obtained in EXAMPLE 6.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] In view of the increasing awareness of insecticide toxicity tohumans and other environmental concerns, it would be advantageous toprovide an active delivery system having an extended release life andhaving a hydrogel material in order that it be non-toxic andbio-degradeable. It would also be advantageous to provide a system forsprayable long lasting active delivery that would be applicable to abroad spectrum of actives thereby eliminating the issue of reactivity ofthe active with one of the membrane components.

[0013] The present invention involves immobilizing active(s) within ahydrogel matrix in a microbead format. Furthermore, the inventionprovides a method of controlling release of active(s) by cyclicallyhydrating and re-hydrating the microbeads. The microbeads of theinvention comprise a matrix forming material, and is preferablysubstantially spherical. The matrix forming materials of the presentinvention are hydrophilic and water soluble. Entrained or finelydispersed within the matrix are micro-sized droplets of active material.Active materials that can be immobilized within the hydrogel microbeadsinclude aldehydes, esters, alcohols, epoxy compounds, ethers, ketones,or combinations thereof. This invention is particularly advantageous fordelivery of reactive ketones in which the double bond of the carbonylgroup is conjugated with one or more double bonds, for exampleacetophenone where the carbonyl group is conjugated with double bonds ofthe aromatic ring.

[0014] Conventional active delivery systems (such as for delivery ofpheromone) generally involve polyurea or polymethyleneureaencapsulation, where interfacial polymerization or in situpolycondensation occurs to provide microencapsulated products,respectively. These systems however, are typically limited toencapsulation of water non-soluble and/or non-alcohol active materials,due to, for example, the reactivity of alcohol with the isocyanatecontained in the polyurea membrane. Surprisingly, it has been found thathydrogel microbeads made from water soluble materials provide sufficientimmobilization of oil soluble actives and alcohol actives such that theactive can be delivered and sprayed by conventional techniques.Furthermore, rather than relying on interfacial encapsulation, thehydrogel microbeads entrap micro-sized droplets of active materialwithin the hydrophilic matrix. This matrix advantageously imparts thecapability of the hydrogel microbeads to immobilize oil-soluble activematerials and minimizes the risk of undesired reactivity between theactive and its immobilizer. Thus, immobilization of active materials byuse of the microbeads of the invention does not render the immobilizedmaterial inert or ineffective.

[0015] A further surprising benefit from immobilizing active ingredientsin hydrogel microbeads is the ability of the hydrogel to “swell” underhumid conditions and shrink under dry conditions. As used herein,“swell” is descriptive of the behavior of a microbead, wherein the size(volume) is enlarged (increased) due to absorption of water. This islikely due to the hydrophilic nature of the matrix forming materialsused to immobilize the active material.

[0016] In the presence of humidity, the hydrogel microbeads aresurprisingly found to be capable of absorbing moisture, rehydrating, andconsequently releasing active material contained within the matrix. Thisbehavior can be cyclical. Thus, by controlling the humidity (or dryness)of the ambient air, the release rate of active material from themicrobeads can be controlled such that specific periods of release canbe generally predicted. It is therefore possible with the presentinvention to release the active material on demand from the microbead.Release on demand, or “smart release,” can be advantageous in thoseinstances where release is preferred at certain times. The microbeads'ability to further release active from the matrix and may increase thelongeveity of releasing effective amounts of active material.Preferably, the microbeads are delivered to an intended environment ineffective amounts to obtain the desired effect. For example, microbeadshaving pheromones entrained therein, are preferably delivered to adesired area in amounts such that mating disruption is effected andrelease is accomplished for more than 4 weeks, more preferably, themicrobead can release for more than about 6 weeks; and most preferablymore than about 8 weeks.

[0017] During the drying process (i.e dehydration) a surface film layerwill form as a result of water evaporation from the matrix. Bothinitially and during use, the microbeads are characterized by a largesurface area to volume ratio, which helps maintain the rate of diffusionof the active material during use. Thus, it has been found thatmicrobeads made according to the method of present invention provideexcellent delivery systems as they are capable of releasing activematerial for extended periods. Furthermore, since the active isdispersed within a water-based matrix, additional protection fromenvironmental conditions (i.e., UV) can be provided.

[0018] Although it has been found that microbeads of the invention canbe made having a diameter of up to about 5 millimeters (mm), it ispreferred that the microbeads be between about 1 micrometers (μm) toabout 1000 μm and more preferably between about 1 μm to about 500 μm indiameter to ensure that the microbeads are easily sprayable fromconventional spray nozzles. Most preferably, to ensure minimal cloggingin conventional nozzles, the microbeads are less than about 400 μm indiameter. It is contemplated, however, that with the advent of largerspray nozzles not currently used in the industry, the microbeads can beprovided in much greater diameters.

[0019] For spraying applications, particularly aerial spraying, it isdesirable that the microbeads be capable of remaining suspended insolution (e.g., water) to ensure that the microbeads do not sink,settle, or coagulate in the suspension. A uniform suspension ensures aneven spray coverage. Preferably, the microbeads of the invention areable to remain in suspension, thus minimizing if not eliminating theneed to agitate during application and optionally storage. Varioussuspension aids can also be included in the suspension containing themicrobeads of the invention. Examples of suitable suspension aidsinclude rhamsam gum, xanthum gum, gellan gum, pectin, and gum arabic.

[0020] Owing to the handling to which the microbeads may be subjected,it is preferable that the microbeads of the present invention should besomewhat elastic, and not frangible. For example, typical atomization ofa suspension during a spray application will force the suspensionthrough two rotating perforated discs that are immediately upstream ofthe discharge nozzle. Sufficient elasticity of the microbeads minimizesphysical damage to the microbeads as they pass through the discs.

[0021] The microbeads of the present invention comprise a matrix formingmaterial and active material. Referring now to FIG. 1, a preferredembodiment is shown, where a plurality of active material droplets 10are entrained within hydrophilic matrix 12. As seen in FIG. 1, activematerial droplets 10 are preferably located between and within matrix12, where matrix 12 provides an immobilizing network around thedroplets. The degree and extent of agitation as well as the type ofsurfactant used to form the microbeads can affect the size and thedispersity of the pheromone droplets within the microbead's matrix.Droplets 10 are preferably can range in size between about 0.01 nm toabout 200,000 nm in diameter. More preferably, the droplets are betweenabout 1 to about 1000 nm in diameter.

[0022] The matrix-forming material useful in the present invention arebiocompatible, water-soluble, have pendant functional groups, andcomplex with ions (e.g., polyvalent cations and/or anions) to formhydrogels. Functional groups of the matrix forming material include forexample, carboxyls, hydroxyls, primary or secondary amines, aldehydes,ketones, esters, and combinations thereof. Preferably the hydrophilicmatrix-forming material can be made from naturally occuringpolysaccharides, such as alginates, chitosans, gums, agars,carrageenans, or the matrix can be made synthetic, water solublemonomers, oligomers or polymers, such as, for example, polyvinylalcohol, poly(N-isoproylacrylamide), acrylamides, acrylates,methacrylates, or combinations thereof.

[0023] Suitable naturally occurring polysaccharides include thewater-soluble salts of alginic, pectic and hyaluronic acids, thewater-soluble salts or esters of polyglucuronic acid, polymanuronicacid, polylygalacturonic acid and polyarabinic acid, and gumkappa-carrageenan. The preferred polysaccharides are the ammonium,magnesium, potassium, sodium and other alkali metal salts of alginicacid, and the most preferred polysaccharide is sodium alginate.

[0024] “Alginate” is the general name given to alginic acid and itssalts. Alginates are composed of D-mannosyluronic (mannuronic—“M”) andL-gulopyranosyluronic (guluronic—“G”) acid residues. The ratio ofmannuronic to guluronic acid residues is known as the M:G ratio. Thealginate used to immoblize active droplets should be carefully selectedto ensure proper microbead formation, ensure the stability of themicrobeads during storage and delivery applications, and ensure that themicrobeads are able to shrink and swell appropriately to deliver thedesired active material over an extended period of time (preferably 4-6weeks). Preferably, an alginate is chosen such that the matrix formed issufficient in strength to withstand the shear forces (conditions) placedupon the microbeads during application via a spray nozzle—i.e., themicrobeads are resistant to rupture during the spray application.

[0025] For strength and stability of the microbeads, it is desirable tochoose the molecular weight and M:G ratio of the alginate to obtainpreferred properties of the ultimate matrix. Although alginates high inmannuronic acid are generally useful for thickening applications,whereas alginates with a high level of guluronic acid are often used forforming gels, both alginate categories (individually or a mixturethereof) are suitable for the microbeads of the invention. A preferredalginate that imparts strength and rupture resistance is an alginatethat has a high level of guluronic acid, e.g., greater than about 30percent by weight. Alginate compositions with excessive levels ofmannuronic acid could result in less stable and less rigid microbeadsthan high guluronic acid gels. However, high mannuronic acid alginatesimpart to the microbeads the capability of swelling and absorbing morewater than microbeads of high guluronic acid content. Thus, a carefulbalance of the advantages imparted by each of M and G residues should beconsidered when choosing a suitable alginate.

[0026] It has been surprisingly found that alginates preferably having amolecular weight in the range of about 100,000 kg/mol to about 2,500,000kg mol, more preferably about 200,000 kg/mol to about 1,500,000 kg/mol.Furthermore, the alginates preferably have an M:G ratio in the range ofabout 0.2 to about 3.5; more preferably about 0.3 to about 1.85.

[0027] Preferred alginates that have a high level of guluronic acid, forexample are alginates from the algae Laminaria hyperborea, stem, wholeplant or frond. Preferred alginates with high levels of mannuronic acidinclude Ascophyllum nodosum, for example.

[0028] Gel matrices formed by crosslinking polysaccharides bearingpendant carboxylate groups are also useful as a preferred class in thepresent invention. These compounds are composed of water-insolublealginates which include, with the exception of magnesium and the alkalimetal salts, the group II metal salts of alginic acid. Thewater-insoluble alginate gels are typically formed by the chemicalconversion of water-soluble alginates in an aqueous solution intowater-insoluble alginates. This conversion usually is accomplished bythe reaction of a water-soluble alginate with polyvalent cationsreleased from a soluble di- or trivalent metal salt.

[0029] Water-soluble alginates can include the ammonium, magnesium,potassium, sodium, and other alkali metal salts of alginic acid.Water-insoluble di- or trivalent metal salts suitable for the presentinvention should satisfy two requirements: (1) that the water-insolublemetal salt contain a di- or trivalent metal ion capable of complexingwith the pendant carboxylate groups of the water-soluble polysaccharideto cause the formation of a water-insoluble polysaccharide gel; and (2)that the water-insoluble metal salt reacts with a water-soluble acid toform a water-soluble metal salt.

[0030] A common and suitable alginate gel is composed of calciumaliginate.

[0031] Sources for the crosslinking calcium ions used in the formationof alginate gels include, for example, calcium carbonate, calciumsulfate, calcium chloride, calcium phosphate, calcium tartrate, calciumnitrate, and calcium hydroxide. Other acceptable crosslinkers mayinclude lanthanum chloride, ferric chloride, cobaltous chloride, asgenerally are other compounds with multivalent cations, such as calcium(Ca++), copper (Cu++), barium (Ba++), strontium (Sr++) and the like.

[0032] The time of gelation of the calcium alginate gels can beaccomplished by regulating the concentration of free calcium ions in thesolution. Typically the concentration of free calcium ions is controlledby manipulation of the ionization rate of the calcium salt and/or by theinclusion of other compounds in the solution which react with the freecalcium ions.

[0033] It has been advantageously found that it is possible toimmobilize a wide range of active materials, including non-water solublematerials as well as alcohols.

[0034] Preferred active materials entrained in the matrix are partiallywater-miscible organic molecules of compounds that have a molecularweight in the range of between about 100 to about 400, preferablybetween about 150 to 3 00. The compounds contain a heteroatom thatconfers some degree of water-miscibility. For many compounds of interestthe sole heteroatom is oxygen, and there may be up to three heteroatomsper molecule in, for instance, hydroxy-substituted or keto-substitutedcarboxylic acids. Unsubstituted carboxylic acids of course contain twooxygen atoms and simple aldehydes, ketones and ethers contain only oneoxygen atom. Compounds that contain nitrogen and/or sulphur atoms arealso of interest.

[0035] Of particular interest are biologically active compounds. Forpurposes of the present invention, the term “biologically active” meansmaterials that affect the life processes of organisms. Materials thatare biologically active include herbicides, pesticides, pharmaceuticals,and semiochemicals, including naturally and artificially producedpheromones and synthetic pheromone analogs. Materials of this naturethat are of particular interest are those materials that interfere witha life process essential to the survival of a target pest.

[0036] The method of the invention can be used to immobilize pheromonewith functional groups such as acetates, aldehydes, ketones, alcohols,ethers, esters, and epoxies. Pheromones may be defined as compoundswhich, when naturally produced, are secreted by one member of an animalspecies which can influence the behavior or development of anothermember of the same animal species. Pheromones generally arespecies-specific and therefore the application of pheromones for insectbehavior modification has minimal effect on non-target pests. Pheromonessupplied for modification of insect behaviour interfere with the “matefinding process” by releasing point sources of pheromone, which maycompete with or camouflage the pheromone plume of a female. This lattertype of action differs from chemical insecticides or insect growthregulators or hormones, in that pheromones target future generations ofinsects, not present ones. As pheromones are very species-specific andare used only in small quantities, their use is more environmentallyacceptable than broadcasting of pesticides.

[0037] Many pheromones have an ester terminal group, for example acetateor formate group. Typically these substances are water-immiscible andincorporation of them into microcapsules by known methods presents noparticular problem. Many other pheromones have an aldehyde or an alcoholterminal group. In general, these are partially water-miscible andpotentially reactive with the reactants used to encapsulate by prior,conventional methods. In particular, it is difficult to achieve highdegrees of encapsulation of materials that have some degree of watersolubility, as the material partitions between the small amount oforganic solvent and the relatively larger amount of water thatconstitutes the continuous phase. Furthermore, these compounds can beexpected to react with the reactants used to encapsulate. Aldehydes andketones react with amines to form aldimines and ketimines, respectively.Alcohols, carboxylic acids and mercaptans react with isocyanates. Epoxycompounds react both with amines and with isocyanates. Thus, the presentinvention overcomes the limitation of delivering partiallywater-miscible substances such as alcohols, aldehydes, carboxylic acids,ketones, ethers, including epoxy compounds, and mercaptans.

[0038] Pheromones useful in the inventive microbeads are preferablyinsect pheromones. In describing the structure of the a pheromone, thefollowing notation is used: the type (E (trans) or Z(cis)) and positionof the double bond or bonds are given first, the number of carbon atomsin the chain is given next and the nature of the end group is givenlast. To illustrate, the pheromone Z-10 C19 aldehyde has the structure;

[0039] Pheromones can be mixtures of compounds with one component of themixture predominating, or at least being a significant component.Partially water-miscible significant or predominant components of insectpheromones, with the target species in brackets, include, for example:E/Z-11 C14 aldehyde (Eastern Spruce Budworm), Z-10 C19 aldehyde (YellowHeaded Spruce Sawfly), Z-11 C14 alcohol (Oblique Banded Leafroller), Z-8C12 alcohol (Oriental Fruit moth) and E,E-8,10 C12 alcohol (Codlingmoth), E-11 C14 acetate (Sparganothis Fruitworm), and Z-11 C14 acetate(Blackheaded Fireworm).

[0040] An example of a ketone that is a pheromone is E or Z7-tetradecen-2-one, which is effective with the oriental beetle. Anether that is not a pheromone but is of value is 4-allylanisole, whichcan be used to render pine trees unattractive to the Southern pinebeetle.

[0041] Preferred embodiments of the invention are described withreference to immobilization of partially water-miscible andwater-immiscible pheromones, but it should be appreciated that theinvention extends to immobilization of materials other than suchpheromones and to microbeads containing materials other than pheromones.Those materials may, or may not, be biologically active.

[0042] For example, alternatively, active materials containingmercaptans can be immobilized in the microbeads of the invention, suchas what is found in urine of animals. These compounds are preferable insituations where animals mark their territory by means of urine, todiscourage other animals from entering the particular territory.Examples of such animals include preying animals such as wolves, lions,dogs, etc. By dispersing hydrogel microbeads containing the appropriatemercaptans, it is possible to define a territory and discourageparticular animals from entering that territory. For example, the urineof a wolf includes a mercaptan, and distribution of microbeads fromwhich this mercaptan is gradually released to define a territory willdiscourage deer from entering that territory. Other active materialsuseful in discouraging approach of animals include essences of garlic,putrescent eggs and capsaicin.

[0043] Other active compounds that can be included in the microbeads ofthe invention include perfumes, fragrances, flavouring agents and thelike.

[0044] Optionally, oil absorbents can be incorporated into the activedroplets. These absorbents can help retain the active droplets withinthe microbeads, resulting in longer lasting formulations. Clays andstarches could alternatively be used for this purpose.

[0045] The concentration of active material in the microbeads of theinvention should be at a level such that the matrix forming material canstill provide a strong, rupture resistant network and deliver aneffective amount of the active material to the environment to which itis intended. Thus, the active material is preferably present in anamount between about 0.1 wt % to about 60 weight percent (wt %) of thetotal weight of the microbead. More preferably, the amount of activematerial is present in the microbead at between about 0.2 wt % to about40 wt %; and most preferably between about 0.3 wt % to about 20 wt %.

[0046] The microbeads of the present invention are preferably deliveredin suspension in aqueous or solvent-based solutions. For environmentaland biologically-friendly reasons, it is preferred that aqueoussuspensions be used. Suspension aids are preferably included in thesuspension formulations to ensure the microbeads remain suspended insolution.

[0047] Preferably, the suspension solution is substantially free ofmonovalent cations, such as sodium, to avoid degradation or breakdown ofthe microbeads. In a preferred aspect, a concentration of approximately50 millimolar of a crosslinker such as calium chloride is maintained ina stored solution comprising the microbeads of the invention.

[0048] Optionally, adhesive material can be included in the compositionsof the invention to assist in retention of the microbeads to an intendedsubstrate. The adhesive material can be provided in various forms, suchas for example, latex or a tacky microspheres. Adherent propertiesimparted to the hydrogel microbeads should result in the microbeadsbeing able to still retain their suspended state and minimizeaggregation or coagulation in the aqueous suspension. Furthermore, anyadhesive material used to impart adherent properties should not affectthe integrity of the particles; it should not dissolve or weaken themicrobead(s).

[0049] A suitable adhesive material that may be included in thecompositions of the invention is adhesive latex. The adhesive latex maybe any suitable water-dispersible adhesive available in the art. In theagricultural business, such latex compositions are often called stickersor spreaders. Stickers are used to help non-encapsulated agriculturechemicals adhere to plants. Spreaders are used to help dispersenon-encapsulated agriculture chemicals on application. Preferredadhesives are acrylate-based adhesives. One suitable latex is availablefrom Rohm & Haas under the trade designation COMPANION. Another isavailable from Deerpoint Industries under the trade designation DPIS-100 (a proprietary sticker/spreader). Examples of such adhesives arepolymers made from the “soft” monomers such as n-butyl acrylate,isooctyl acrylate, or the like, or copolymers made from a softcomponent, such as isobutylene, n-butyl acrylate, isooctyl acrylate,ethyl hexyl acrylate, or the like; and a polar monomer such as acrylicacid, acrylonitrile, acrylamide, methacrylic acid, methyl methacrylateor the like. Non-spherical polyacrylate adhesives are commerciallyavailable, for example, as the Rohm and Haas RHOPLEX line of adhesives.Preferably, the non-spherical polyacrylate adhesive is present in anamount of about 10-35% by weight of the total suspension.

[0050] Tacky microspheres of adhesive may alternatively be used to helpadhere the hydrogel microbeads of the invention to an intendedsubstrate. The tacky microspheres have sufficient adhesive properties toprovide the desired adhesive function, yet there is no danger ofcompletely coating the microbead which may lead to potentiallyinhibiting the release characteristics of the microbead. The combinationof microbeads and tacky microspheres may be applied without the need tomodify the orifices of conventional sprayers with minimal clogging orplugging problems. Furthermore, the incorporation of tacky (adhesive)microspheres to the (formulation) suspension of microbeads allows themicrobeads' surfaces to become tacky. The beads can therefore stick tointended surfaces, such as, foliage and branches, for example. Theadhesive microspheres, especially if they are hollow, may also absorbsome of the active material into its own body, thus providing a secondmechanism of release of the active material. This could result in anoverall alteration, preferably an enhancement, of the release profile.

[0051] Preferably, the adhesive material is an acrylate- ormethacrylate-based adhesive system comprising infusible, solventdispersible, solvent insoluble, inherently tacky, elastomeric copolymermicrospheres as disclosed in U.S. Pat. No. 3,691,140. Alternatively,this adhesive composition may comprise hollow, polymer, acrylate,infusible, inherently tacky, solvent insoluble, solvent dispersible,elastomeric pressure-sensitive adhesive microspheres as disclosed inU.S. Pat. No. 5,045,569. Other suitable adhesives are the tackymicrospheres having pendant hydrophilic polymeric or oligomeric moietiesthat are disclosed in U.S. Pat. No. 5,508,313.

[0052] Alternatively, the adhesive comprises between about 60-100% byweight of hollow, polymeric, acrylate, inherently tacky, infusible,solvent-insoluble, solvent-dispersible, elastomeric pressure-sensitiveadhesive microspheres having a diameter of at least 1 micrometer, andbetween about 0-40% by weight of a non-spherical polyacrylate adhesive.The hollow microspheres are made in accordance with the teaching ofEuropean Patent Application 371,635.

[0053] The compositions of the present invention may also include one ormore adjuvants including, for example, gelling aids, preservatives,dyes, humectants, UV protectants, fixatives, emulsifiers, extenders, andfreeze/thaw stabilizers such as polyhydric alcohols and their esters.These materials are present in an amount effective to achieve theirextended function, generally less than about 5% typically less than 2%,by weight of the composition.

[0054] Incorporation of a light stabilizer can be included in themicrobeads of the invention. Suitable light stabilizers include thetertiary phenylene diamine compounds disclosed in Canadian Patent No.1,179,682, the disclosure of which is incorporated by reference. Thelight stabilizer can be incorporated by dissolving it, with the active,in a water-immiscible solvent. Alternatively, a light stabilizer can beincorporated in the microbeads as taught in Canadian Patent No.1,044,134, the disclosure of which is also incorporated by reference.

[0055] The process of making the microbeads of the invention, preferablycomprises, initially, the formation of a microemulsion and thedispersion of the active material in the hydrogel material. Themicroemulsion is then mechanically atomized to create substantiallyspherical droplets which are subsequently gelled (hardened) to form ahydrogel microbead having an active material dispersed therein.

[0056] In a preferred method of making the microbeads of the invention,an emulsion of an oil active within a water soluble solution comprisinga hydrogel is first formed. This emulsion is then followed by amechanical microbead forming step that can be performed by, for example,spray method or emulsification. The droplets are then hardened or curedeither by chemical means (i.e., polymer cross-linking) or bynon-chemical means (i.e., temperature, pH, pressure). The resultingmicrobead is a hydrogel microbead, having greater than about 30% waterinitially, and the active would be finely dispersed and entrained withinthe water-polymer matrix. The size of the microbeads is generallygoverned by the intrinsic properties of the emulsion solution, the feedrate and the coaxial airflow rate.

[0057] The droplets which are atomized can then be allowed to free-falldirectly into a reacting bath. The reacting bath cures or sets thehydrogels so that they solidify. Reaction bath curing can be achievedthrough chemical or non-chemical means. For the case of sodiumalginates, calcium ions are used to cross-link the polymer chains. Apreferred crosslinker is calcium chloride.

[0058] The emulsification method is another technique that can be usedfor producing hydrogel microbeads. In selecting the continuous phasematerial, it is prefered that it be immiscible with both the aqueouspolymer and oil active.

[0059] The matrix-forming material preferably has a range ofconcentrations usable in practicing the invention. The concentrationshould be chosen to optimize ease of handling, gelling time, thestrength of the hydrogel microbead around the active material droplets.For example, a sodium alginate solution can preferably be prepared in aconcentration of about 1 to about 10% (w/v) in water, more preferablyabout 1.5 to about 5% and most preferably from about 1 to 3%. However,if the hydrogel agent concentration is too great, the solution may be soviscous as to hinder the formation of spherical microbeads.

[0060] Alternatively, hydrogel microbeads of the invention can beformed, for example, by adding the matrix forming material solutiondrop-wise to a selected crosslinker. For example, a method can be usedwhereby droplet formation and crosslinker addition is completed as a onestep process by a vibrating nozzle which ejects a hydrogel droplet fromone source and coats the droplet with a crosslinker from another. U.S.Pat. No. 4,701,326 teaches use of this method.

[0061] In the preferred aspect where alginates are used to immobilize anactive material, a crosslinker is preferably made up in solution at aconcentration of 1 to 1000 millimolar, more preferably 20 to 500millimolar and most preferably from 50 to 100 millimolar. Theconcentration ranges may have to be adjusted, depending on the nature ofa crosslinker and matrix-forming material.

[0062] The microbeads comprising matrix material and active material canbe treated with the crosslinker solution by soaking, spraying, dipping,pouring or any of several other methods which will deposit an amount ofthe complexing agent on the droplet. When soaking, the time in solutionmay be from 1 second to 24 hours, preferably 1 minute to 1 hour, andmore preferably from 10 to 30 minutes.

[0063] The temperature for hydrogel microbead formation is preferablychosen as to avoid damage or alteration to the active material. Forexample, in the preferred aspect where alginates are utilized, thetemperature is preferably in the range of about 1° C. to about 70° C.;more preferably between about 10° C. to about 40° C., and mostpreferably between about 15° C. to about 30° C.

[0064] Surfactants can be used in the process of forming the microbeadsin effective amounts to enhance droplet formation of the active in thecontinuous phase of the matrix forming material solution. Theincorporation of different surfactants will offer different types ofmicroemulsion drop sizes of the active within the hydrogel as well asdictate the amount of free oil lost in the reacting bath solution. Apreferred surfactant has a high critical micelle concentration, such asfor example, a product available under the product designation DISPONILSUS IC 875 (CMC˜1%)., available from Henkel (Ambler, Pa.).

[0065] Particularly preferred surfactants are nonionic. Examples ofsuitable surfactants include polyvinylpyrrolidone (PVP) andpoly(ethoxy)nonylphenol. PVP is usable and available at variousmolecular weights in the range of from about 20,000 to about 90,000. PVPhaving a molecular weight of about 40,000 is preferred.Poly(ethoxy)nonylphenols are commercially available under the tradedesignation IGEPAL from Rhone-Poulenc (Cranbury, N.J.), with variousmolecular weights depending on the length of the ethoxy chain.Poly(ethoxy)nonylphenols having the formula:

[0066] where n has an average value from about 9 to about 13 can beused. A preferred poly(ethoxy)nonylphenols is available commerciallyunder the product name IGEPAL 630, from Rhone-Poulenc (Cranbury,N.J.)—630 is indicative of the approximate molecular weight of thecompound. Other examples of suitable surfactants include polyether blockcopolymers, such as those available under the trade designationsPLURONIC and TETRONIC, both available from BASF (Washington, N.J.),polyoxyethylene adducts of fatty alcohols, such as BRIJ surfactantsavailable from ICI (Wilmington, Del.), and esters of fatty acids, suchas stearates, oleates, and the like. Examples of such fatty acidsinclude sorbitan monostearate, sorbitan monooleate, sorbitansesquioleate, and the like. Examples of the alcohol portions of thefatty esters include glycerol, glucosyl and the like. Fatty esters arecommercially available as surfactants under the trade designationARLACEL C from ICI (Wilmington, Del.)

[0067] Various properties of the surfactant, such as for example, chainlength, functional groups, and hydrophobic regions, can affect the sizeof the active droplets formed within the microbeads. For example, use ofPVP (having a molecular weight of 40,000) tend to result in productionof larger sized active droplets than use of poly(ethoxy)nonylphenols(IGEPAL 630).

[0068] Ionic surfactants can alternatively be used in the processes ofthe invention. Examples of suitable ionic surfactants partiallyneutralized salts of polyacrylic acids such as sodium or potassiumpolyacrylate or sodium or potassium polymethacrylate.

[0069] The active material entrained in the microbeads of the inventionare released in air gradually over time. This is in contrast toconventional micro-encapsulated materials that could potentially releasethe active ingredient nearly all at one time, for example at the time ofshell rupture. Active release from the microbeads of the invention hassurprisingly been found to be controllable by controlling the humidity(and dryness) of the environment in which the microbeads are in.

[0070] While not being bound by this theory, it is believed that themechanism of release involves water evaporation from the gel and thendiffusion of active through the hydrogel matrix. Alternatively, theactive may become entrained in the water from the matrix, and as thewater evaporates, the active releases into the atmosphere.

[0071] In preferred applications, the hydrogel microbeads would besprayed followed by water evaporation within the gel. As the hydrogelbead dehydrates, the matrix shrinks in size and releases its active withtime. The degree of shrinkage of the microbead from its original size,depending on the components used in the formulation. Preferably, themicrobeads shrink about 10 to about 90% from its original size, morepreferably from about 40 to about 80%, and most preferably from about 50to about 70%.

[0072] Advantageously, the microbead, upon re-exposure to humidity, canswell and rehydrate itself by absorbing water. Re-exposure to humiditycan be performed in various ways. For example the microbeads' surfacescan be contacted directly with water or other aqueous solutions. Inagricultural applications, a farmer or caretake can irrigate the plantsand foliage to re-hydrate the hydrogel microbeads. Alternatively, thehumidity of the environment or ambient air in which the microbeads arelocated in can be increased by entraining air droplets in the air. Thus,the microbeads can be “re-activiated” by re-hydration, therebyselectively controlling the release times of the active material.

[0073] The microbeads of the invention can be delivered to an intendedsubstrated by various methods. In the preferred embodiment where theactive material is a pheromone, delivery of the microbeads will dependon various factors, such as for example, the size of release coveragedesired. For small concentrated areas, the microbeads can be impregnatedinto hollow fibres, plastic laminate flakes or twist-ties and then thefibers or ties are physically attached to plants to be protected frominsect infestation. For larger areas, spraying (aerially or e.g., byback-pack carried personal spray units) may be the better option.

[0074] All patents cited in this specficiation are hereby incorporatedby reference.

[0075] The following examples are provided to illustrate, but not limit,the scope of the invention. Unless otherwise specified, all parts andpercentages are by weight.

EXAMPLES

[0076] The following list of materials were used in the Examples. Listedadjacent to each material is the manufacturer and/or supplier from whichthe materials were obtained. 3M HFE 7100 3M Co. (St. Paul, MN) CarvoneBedoukian (Danbury, CT) Disponil SUS IC 875 Henkel (Ambler, PA) Drakeol34 Penreco (Karns City, PA) E,E-8,10-C12 alcohol Shin-Etsu Chemical Co.,Ltd. (Tokyo, Japan) Igepal C0-630 Rhone-Poulenc (Cranbury, New Jersey)Menthone Berjé (Bloomfield, NJ) Paraffin Wax Aldrich Chemical Co.(Milwaukee, WI) Sodium alginate SKW (Lannilis, France) Solvent 100 ShellChemical Co. (Bayway, NJ) Starch Aldrich Chemical Co. (Milwaukee, WS)Tixogel EZ100 Süd-Chemie Rheologicals (Louisville, KY) Z11-C14 acetateShin-Etsu Chemical Co., Ltd. (Tokyo, Japan)

Test Methods

[0077] To evaluate the physical performance of microbeads of theinvention, two parameters were measured: (1) air concentrations ofpheromone released from the microbead formulation and (2) the amount ofactive remaining (i.e., residual concentration) in the microbead overtime.

[0078] Air Concentration Determination

[0079] A known amount of beads (10 microbeads) were recovered and placedin a constant airflow chamber of 100 mL/min (˜23-24° C. temperature).The effluent air stream from the chambers was analyzed for activeconcentration using solid phase microextraction (SPME) (Supelco,Bellefonte, Pa.) and gas chromatography (GC) (Varian ChromatographySystems, Walnut Creek, Calif.) over a period of weeks to evaluate theperformance of the hydrogel microbeads.

[0080] To calculate the Release Rate of an active, the Air Concentrationis multiplied by the Air Flow rate.

[0081] Residual Concentration Determination

[0082] Formulations were filtered using a Buchner type vacuum funnel,washed with room temperature distilled water and dried in a fumehood atroom temperature for 24 hours. Fifty milligrams of the dried formulationwere put on tinfoil squares as application substrates. After therequired exposure time, the microbeads were subjected to extraction forat least 24 hours with 4 mL of dichloromethane to determine the residuallevel of active still remaining in the formulation. Each collectedsample was then analyzed by gas chromatography.

Example 1

[0083] For each of the samples A-I, a sodium alginate solution wasinitially prepared by dissolving a preweighed amount of alginate into aknown volume of distilled water. The solution was mixed thoroughly tosolubilize the polymer and was deaerated for removal of entrained airbubbles. In a separate 250 mL vessel, the active and surfactant wasadded and mixed at a speed of about 2000 RPM using a marine typeimpeller (3.81 cm diameter). To the mixture, the alginate solution wasgradually added to form the microemulsion. The emulsion was homogenizedfor about 30 minutes. The emulsion was then atomized into fine particledroplets using a coaxial air nozzle sprayer. The size of the particleswas determined by the settings on the atomizing device. This involvedcontrol of the nozzle head diameter, the feed rate of the emulsionthrough the nozzle and the airflow which passed along its feed path(shown in Table 2).

[0084] Samples A-E demonstrated the ability of this invention toencapsulate oils or pheromones with function groups of ketones,alcohols, and acetates. All the formulations resulted in substantiallyspherical intact hydrogel microbeads containing the desired active.

[0085] Samples F-H demonstrated the ability of this invention toabsorbed oils or pheromones with function groups of ketones, alcohols,and acetates within an absorbent material prior to encapsulation withina hydrogel matrix. All the formulations resulted in substantiallyspherical intact hydrogel microbeads containing the desired active.

[0086] Sample I incorporated an adhesive material, 3M MicrosphereAdhesive Suspension (as described in U.S. Pat. No. 5,508,313, example 2having a ratio of IOA:AA:Carbowax of 97:2:1) within hydrogel microbeadscontaining no active material. The addition of adhesive material in thehydrogel formulation allowed the particles to become tacky and stickywhen dried. TABLE 1 Hydrogel microbead formulations Sodium alginateActive Surfactant Calcium Conc. Weight Weight Weight conc. Sample (g/100mL) (g) Type (g) Type (g) (mM) A 2.0 50.0 Carvone 20.0 Igepal 2.0 50CO-630 B 2.0 38.6 E,E-8,10- 1.0 Disponil 1.0 50 C12 alcohol/ SUS ICSolvent 100 875 (1:4 by wt) C 2.5 250.0 Menthone 50.0 Igepal 5.0 50CO-630 D 2.0 38.6 Z11-C14 1.0 Disponil 0.4 50 acetate SUS IC 875 E 2.5800.0 Z11-C14 20.0 Igepal 2.0 1000 acetate CO-630 F 2.0 40.0 Z11C14 3.0n/a 50 acetate/ starch (1:4 by wt) G 2.5 250.0 Menthone/ 56.0 n/a 50Tixogel EZ100 (8:1 by wt) H 2.5 250.0 Menthone/ 44.0 n/a 50 parffin wax(10:1 by wt) I 2.0 100.0 3M 10.0 n/a 50 Microsphere Adhesive

Example 2

[0087] Hydrogel microbeads were formed using coaxial airflowatomization, using the formulations of Samples A and E. Average particlediameters were measured by evaluating 30-50 microbeads, using astereomicroscope product name STEREOZOOM 7 available from Bausch & Lomb(Brick, N.J.) and a light microscope product LEITZ DIAPLAN availablefrom Ernst Leitz (Wetzlar, West Germany). The nozzle size and settingsvaried respectively to produce different size particles. TABLE 2 FeedNozzle Coaxial air Mean Diameter Pressure Diameter Pressure DiameterSample (mm) (kPa) (mm) (kPa) (mm) A 0.508 68.9 1.17 0 2.8 0.406 137.91.17 0 1.7 0.508 68.9 1.17 34.5 0.9 0.406 137.9 1.17 34.5 0.2 E 0.50834.4 1.40 34.5 0.094 0.508 110.3 1.40 13.8 0.135 0.508 110.3 1.40 34.50.125 0.508 96.5 1.40 27.6 0.064

Example 3

[0088] Following the test methods described above for Air Concentration,the known batches from Sample E of Example 1 were evaluated over aduration of of 24 days. Table 3 provides the release rate analysis.Laboratory formulation evaluation studies entailing residual analysisdemonstrated that a minimum of four week sustained release of an active(pheromone Z11-C14 acetate) from a hydrophilic matrix (calcium alginate)was achieved. Air Concentration Determination analysis showed a burst ofactive (pheromone) in the air during the first week of release followedby a gradual decrease with time. Low levels of released pheromone werestill being detected from the hydrogel microbeads after 3 weeks TABLE 3Time Release Rate of Z11-C14 acetate from Example (days) 2, Sample Bhaving 64 μm dia. (ng/min) 0.00 — 0.04 39.93 0.1 1372.52 3.0 695.26 4.1325.96 4.8 119.53 6.8 131.27 10.0 95.34 10.9 75.37 17.1 0.10 18.0 0.1321.0 0.34 24.0 0.22

Example 4

[0089] The four batches from Example 2 (Formulations from Sample E) wereevaluated for Residual Concentration (i.e., amount of active left in themicrobead) for 50 days. Table 4 provides the results. TABLE 4 % ResidualZ11-C14 acetate in hydrogel microbeads formed by Example 2, FormulationSAMPLE E Time 64 microns 94 microns 125 microns 135 microns (days) MeanRSD Mean RSD Mean RSD Mean RSD 0 100.0 11.0 100.0 4.0 100.0 17.0 100.021.0 2 96.7 6.0 — — 96.5 28.0 97.9 4.0 10 82.4 11.0 78.2 2.0 44.9 15.068.3 11.0 18 60.7 3.0 — — 24.8 8.0 43.6 13.0 25 56.3 14.0 37.5 7.0 23.66.0 47.3 11.0 40 32.0 7.0 26.9 3.0 11.7 4.0 13.5 2.0 47 15.2 1.0 23.13.0 4.5 3.0 9.5 5.0

Example 5

[0090] Hydrogel Encapsulation by Emulsification Method

[0091] For each of Samples J and K, a sodium alginate solution wasinitially prepared by dissolving a preweighed amount of alginate into aknown volume of distilled water. The solution was mixed thoroughly tosolubilize the polymer and was deaerated for removal of entrained airbubbles. Active and absorbent were mixed together and allowed to sitovernight. The active/absorbent mixture, surfactant, calcium carbonate,and polymer forming matrix solution were homogenized using a marine type(3.81 cm diameter) impeller at a speed of 1800 RPM for 10 minutes. Theemulsion was added to a 1 liter baffled glass reactor containingcontinous phase fluid. The mixing impeller was a disk turbine agitator(5.1 cm diameter) and the mixture was emulsified at a speed of about1800 RPM. After 10 minutes, slow dropwise addition of the pH reducer wascommenced to set the gel. The stirring was continued for 10 minutes,then 200 g of a 50 millimolar calcium chloride solution was poured intothe reactor and continued mixing for an additional 10 minutes. Discretespherical microbeads were produced with a particle size range of 4-200microns. TABLE 5 pH reduction Sodium alginate Glacial Conc. Active CaCO₃Surfactant Continuous phase acetic acid (g/100 Weight Weight weightWeight Weight weight Sample mL) (g) Type (g) (g) Type (g) Type (g) (g) J2.0 50.0 Carvone/ 30.0 0.50 N/A Drakeol 500.0 30.0 Tixogel E/Z100 34(5:1) K 2.0 25.0 Carvone/ 28.0 0.25 Span 1.0 3M HFE 1000.0 20.0 TixogelE/Z100 85 7100 (5:0.6)

Example 6

[0092] Humidity Study

[0093] To humidify the airflow entering the flow chamber, a waterreservoir was placed in between the airline feed and the flow chamber.As air traveled over the water reservoir, it entrained moisture thushumidifying the airflow. The humidity level under normal room conditionsranged from 20-30% relative humidity. Under water entrained conditions,the relative humidity level of the air in the chambers ranged from40-95%.

[0094] For the humidity study, an active, carvone, was used to model therelease from calcium alginate hydrogel microbeads. FIG. 2 shows theamount of active released by the microbeads, as measured using the AirConcentration Determination Test described above. As shown in FIG. 2,from microbeads of the Sample J formulation, the initial release wasobserved followed by a constant release with time. In the presence ofhumidity regions 20 and 22, the hydrogels absorbed the moisture from theair and released more active contained within the matrix. Thisshrink/swell behavior was found to be cyclical, depending on whether theair was dry or humid.

What is claimed is:
 1. A method of delivering and releasing activematerial comprising the steps of: a) entraining a plurality of activematerial droplets within a hydrophilic matrix inside a hydrogelmicrobead; b) suspending a plurality of said microbeads in a solution;c) delivering said solution comprising said microbeads onto a substrate;and d) allowing said microbeads to dehydrate.
 2. The method according toclaim 1 further comprising the steps of: e) exposing said microbeads tohumidity; and f) allowing said microbeads to rehydrate.
 3. The methodaccording to claim 1 wherein said active material is a pheromone andsaid hydrophilic matrix is an alginate.
 4. The method according to claim2 wherein said step of exposing said microbeads to humidity is performedby wetting the surfaces of said microbeads with a solution.
 5. Themethod according to claim 2 wherein said step of exposing saidmicrobeads to humidity is performed by adding moisture to the ambientair.
 6. The method according to claim 2 wherein said steps d) thru f)are repeated sequentially.
 7. The method according to claim 1 whereinsaid hydrophilic matrix is made from a polysaccharide.
 8. The methodaccording to claim 7 wherein said polysaccharide is selected from thegroup consisting of alginate, chitosans, carrageenan, gum and agar. 9.The method according to claim 1 wherein said hydrophilic matrix is amaterial selected from the group consisting of polyvinyl alcohol,poly(N-isopropylacrylamide), acrylamides, acrylates, methacrylates, andcombinations thereof.
 10. The method according to claim 1 wherein saidactive material is selected from the group consisting of pheromone,mercaptan-containing compound, herbicide, pesticide, and pharmaceuticalmaterial.
 11. The method according to claim 1 wherein said microbead hasan average diameter between about 1 μm to about 1000 μm.
 12. The methodaccording to claim 1 wherein said microbead has an average diameterbetween about 1 μm to about 500 μm.
 13. The method according to claim 1wherein said microbead further comprises a surfactant.
 14. The methodaccording to claim 1 wherein said microbead further comprises an oilabsorbent.
 15. The method according to claim 1 wherein said microbeadsfurther comprise an additive selected from the group consisting ofpreservatives, humectants, stabilizers, UV protectants, and combinationsthereof.
 16. The method of claim 1 wherein said active material ispresent in an amount between about 0.1 wt % to about 60 wt % of thetotal weight of said microbead.
 17. The method of claim 1 wherein saidactive material is present in an amount between about 0.2 wt % to about40 wt % of the total weight of said microbead.
 18. The method of claim 1wherein said active material is present in an amount between about 0.3wt % to about 20 wt % of the total weight of said microbead.
 19. Asprayable composition comprising microbeads suspended in a solution,wherein said microbeads comprise a hydrophilic matrix having a pluralityof active material droplets entrained therein.
 20. The composition ofclaim 19 wherein said hydrophilic matrix is made from a polysaccharide.21. The composition of claim 19 wherein said polysaccharide is selectedfrom the group consisting of alginate, chitosans, carrageenan, gum andagar.
 22. The composition of claim 19 wherein said hydrophilic matrix isa material selected from the group consisting ofpoly(N-isopropylacrylamide), acrylamides, acrylates, methacrylates, andcombinations thereof.
 23. The composition of claim 19 wherein saidactive material is selected from the group consisting of pheromone,mercaptan-containing compound, herbicide, pesticide, and pharmaceuticalmaterial.
 24. The composition of claim 19 wherein said microbead has anaverage diameter between about 1 μm to about 1000 μm.
 25. Thecomposition of claim 19 wherein said microbead has an average diameterbetween about 1 μm to about 500 μm.
 26. The composition of claim 19wherein said active material is present in an amount between about 0.1wt % to about 60 wt % of the total weight of said microbead.
 27. Thecomposition of claim 19 wherein said active material is present in anamount between about 0.2 wt % to about 40 wt % of the total weight ofsaid microbead.
 28. The composition of claim 19 wherein said activematerial is present in an amount between about 0.3 wt % to about 20 wt %of the total weight of said microbead.
 29. The composition of claim 19further comprising adhesive material selected from the group consistingof hollow tacky adhesive microspheres, solid tacky adhesivemicrospheres, latex, and combinations thereof.
 30. The composition ofclaim 19 wherein said microbeads further comprise a surfactant.
 31. Thecomposition of claim 19 wherein said microbeads further comprise an oilabsorbent.
 32. The composition of claim 19 wherein said microbeadsfurther comprise an additive selected from the group consisting ofpreservatives, humectants, stabilizers, UV protectants, and combinationsthereof.